Demyelination-Induced Inflammation Attracts Newly Born Neurons to the White Matter

There is compelling evidence that microglial activation negatively impacts neurogenesis. However, microglia have also been shown to promote recruitment of newly born neurons to injured areas of the gray matter. In the present study, we explored whether demyelination-triggered inflammation alters the process of neurogenesis in the white matter. A 2-μl solution of 0.04 % ethidium bromide was stereotaxically injected into the corpus callosum of adult male rats. Brain inflammation was dampened by daily injections of progesterone (5 mg/kg, s.c.) for 14 days. Control rats received oil (s.c.). Newly born neurons (DCX and Tbr2), microglia (Iba-1), astrocytes (vimentin or GFAP), oligodendrocyte progenitor cells (OPCs; NG2), and mature oligodendrocytes (CC-1) were monitored in the vicinity of demyelination site using immunofluorescent staining. Western blot was used to explore microglial polarization using M1 (iNOS) and M2 (arginase-1) markers. Focal demyelination elicited strong microglial and astroglial activation and reduced the number of OPCs at the site of demyelination. This inflammatory response was associated with enhanced number of newly born neurons in the white matter and the subventricular zone (SVZ). A proportion of newly born neurons within the white matter showed features of OPCs. Interestingly, blunting brain inflammation led to reduced neurogenesis around the demyelination area and in the SVZ. These data suggest that the white matter inflammation creates a conducive environment for the recruitment of newly born neurons. The fact that a sizable fraction of these newly born neurons adopt OPC features suggests that they could contribute to the remyelination process.     

Quality of Life in Rural Communities: Residents Living Near to Tembeling,Pahang and Muar Rivers,Malaysia

The main aim of this study is to identify the quality of life (QoL) among communities residing near the Tembeling, Pahang and Muar Rivers in Malaysia. This quantitative study used a constructed questionnaire as main tool to collect data on the QoL of river communities. A total of 240 villagers were selected as respondents. The results indicated that the dimensions of settlement, safety, involvement and social relationships, as well as education scored highest, while dimensions of physical environment, financial and job security yielded moderate scores. Dimensions of infrastructure facilities yielded a low mean score. Recommendations are provided, in the hope that our results may be useful for strategies that could enhance QoL of these river communities.     

Bacterial l-asparaginases for cancer therapy: Current knowledge and future perspectives

l -Asparaginases hydrolyzing plasma l -asparagine and l -glutamine has attracted tremendous attention in recent years owing to remarkable anticancer properties. This enzyme is efficiently used for acute lymphoblastic leukemia (ALL) and lymphosarcoma and emerged against ALL in children, neoplasia, and some other malignancies. Cancer cells reduce the expression of l -asparaginase leading to their elimination. The l -asparaginase anticancerous application approach has made incredible breakthrough in the field of modern oncology through depletion of plasma l -asparagine to inhibit the cancer cells growth; particularly among children. High level of l -asparaginase enzyme production by Escherichia coli, Erwinia species, Streptomyces, and Bacillus subtilis species is highly desirable as bacterial alternative enzyme sources for anticancer therapy. Thermal or harsh conditions stability of those from the two latter bacterial species is considerable. Some enzymes from marine bacteria have conferred stability in adverse conditions being more advantageous in cancer therapy. Several side effects exerted by l -asparaginases such as hypersensitivity should be hindered or decreased through alternative therapies or use of immune-suppressor drugs. The l -asparaginase from Erwinia species has displayed remarkable traits in children with this regard. Noticeably, Erwinia chrysanthemi l -asparaginase exhibited negligible glutaminase activity representing a promising efficiency mitigating related side effects. Application of software such as RSM would optimize conditions for higher levels of enzyme production. Additionally, genetic recombination of the encoding gene would indisputably help improving enzyme traits. Furthermore, the possibility of anticancer combination therapy using two or more l -asparaginases from various sources is plausible in future studies to achieve better therapeutic outcomes with lower side effects.     

The impact of local surface changes in Borneo on atmospheric composition at wider spatial scales: coastal processes, land-use change and air quality

We present results from the OP3 campaign in Sabah during 2008 that allow us to study the impact of local emission changes over Borneo on atmospheric composition at the regional and wider scale. OP3 constituent data provide an important constraint on model performance. Treatment of boundary layer processes is highlighted as an important area of model uncertainty. Model studies of land-use change confirm earlier work, indicating that further changes to intensive oil palm agriculture in South East Asia, and the tropics in general, could have important impacts on air quality, with the biggest factor being the concomitant changes in NO(x) emissions. With the model scenarios used here, local increases in ozone of around 50 per cent could occur. We also report measurements of short-lived brominated compounds around Sabah suggesting that oceanic (and, especially, coastal) emission sources dominate locally. The concentration of bromine in short-lived halocarbons measured at the surface during OP3 amounted to about 7 ppt, setting an upper limit on the amount of these species that can reach the lower stratosphere.     

The alanine-serine-cysteine-1 (Asc-1) transporter controls glycine levels in the brain and is required for glycinergic inhibitory transmission

Asc-1 (SLC7A10) is an amino acid transporter whose deletion causes neurological abnormalities and early postnatal death in mice. Using metabolomics and behavioral and electrophysiological methods, we demonstrate that Asc-1 knockout mice display a marked decrease in glycine levels in the brain and spinal cord along with impairment of glycinergic inhibitory transmission, and a hyperekplexia-like phenotype that is rescued by replenishing brain glycine. Asc-1 works as a glycine and L-serine transporter, and its transport activity is required for the subsequent conversion of L-serine into glycine in vivo. Asc-1 is a novel regulator of glycine metabolism and a candidate for hyperekplexia disorders.     

A pilot study on the relation between irisin single-nucleotide polymorphism and risk of myocardial infarction

BackgroundMyocardial infarction (MI) is the major cause of death and disability worldwide. Many recent studies revealed the relationship between circulating irisin levels, endothelial dysfunctions and subclinical atherosclerosis in adult patients.ObjectivesThe aim of this study was to investigate the distribution of Irisin gene single nucleotide polymorphism in patients with MI and its association with other clinical and laboratory variables in these patients.Patients and methodsThis study was carried out in 100 patients with MI, and 100 healthy subjects served as controls. All studied subjects underwent laboratory investigations, including measurement of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c) high-density lipoprotein cholesterol (HDL-c), creatinine kinase-MB (CK-MB), troponin I (TnI) and genotyping of rs 3480 and rs726344 of Irisin genes using the TaqMan Allelic Discrimination assay technique.ResultsThere was a significant difference of Irisin genotypes in patients when compared to controls. By estimating odd ratio (OR) an association was found between G allele of rs 3480 and A allele of rs726344with increase the risk of developing myocardial infarction by 4.03 and 3.47 fold respectively. GG of rs 3480 carriers had significantly increased Troponin I and triglyceride levels, while GA carriers of rs726344 had significantly increased CKMB, Total cholesterol, LDLc, HDLc, troponin I and triglyceride levels compared with other genotypes.ConclusionG allele of rs 3480 and A allele of rs726344can considered as genetic risk factors for MI; these findings could have an impact on preventive strategy for myocardial infarction.     

A survey of therapeutic drug monitoring in a teaching hospital

ObjectivesTherapeutic drug monitoring (TDM) is one of the tools that aim to improve and ensure the best therapeutic effects while avoiding drug toxicity. This study aimed to identify the clinical utilization and application of TDM at a major teaching hospital in Jeddah.MethodsA cross sectional survey of the clinical utilization and application of TDM at King Abdulaziz University Teaching Hospital across nurses in medical, surgical, pediatric, and intensive care units. The sample size (n = 130) represented 30% of the nursing population. The collection of questionnaires started on the 31st of January 2019 and was completed by the 10th of March 2019.ResultsThe indication to use TDM was well-known to respondents. However, only 64% of respondents reported collection and measuring of the correct drug levels at a precise sampling time with no specific protocols being followed for each drug. Moreover, only 53% reported that the drug levels were being re-measured and adequately monitored for the right indication and proper sampling time. Regarding the presence of clinical pharmacists, 70% of the respondents indicated that no clinical pharmacist worked in their department.ConclusionResults demonstrate that appropriate sampling time was not used for the majority of monitored drugs. In the absence of a TDM request form, this finding probably indicates the lack of national or local TDM guidelines. In conclusion, TDM services, which include standardized forms, references, and an active clinical pharmacist will likely improve the application of TDM.     

Genetic diversity of <Emphasis Type="Italic">Opuntia</Emphasis> spp. varieties assessed by classical marker tools (RAPD and ISSR)

Opuntia, commonly named “nopal” in Mexico, is an important crop for its agronomical, economical, ecological and cultural value. Furthermore, it is known for its taxonomic complexity. In this paper, we report the genetic variability of 52 Opuntia cultivars with agronomic and economic importance, classified into 12 different species using random amplified polymorphic DNA (RAPD) and inter-simple sequence repeats (ISSR) markers. Ten primers, five for each marker type, were selected to assess their ability to detect polymorphisms in this plant accesions/varieties. Both marker systems generated a total of 307 bands, of which 50.8 % were polymorphic with an average of 15.6 polymorphic bands per primer. Thus, we assume that Mexican Opuntia varieties present broad genetic variation. Based on percentage of polymorphic bands; resolving power; polymorphic information content; and Marker Index, the K-12 (RAPD) and IS-06 (ISSR) primers were the most informative ones. Clusters obtained from RAPD, ISSR and a combination of both data sets did not match the actual taxonomic classification. On the other hand, the putative varieties currently classified in the same species were not located in the same cluster. Besides, the varieties included in O. ficus-indica, O. albicarpa and O. megacantha showed broad variation but were not well defined into separate clades; these cultivars possibly have common ancestry. The results presented here support our hypothesis about the existence of a smaller number of Opuntia species in accordance with those currently described, but with high intraspecific genetic variation.     

Vessel development and the importance of lateral flow in water transport within developing bundles of current-year shoots of grapevine (<Emphasis Type="Italic">Vitis vinifera</Emphasis> L.)

In the developing xylem bundles of young stems, the presence of immature living vessel elements can strongly restrict or even block axial hydraulic conductance, especially in newly matured vessels. Lateral connections between vessels may provide an alternative pathway for water movement to bypass these closed, living elements. Using the grapevine as a model system, the present study aimed to demonstrate the effects of living vessel elements on water movement patterns, and the importance of lateral flow for effective water conductivity in the developing bundles. Living vessel elements were detected using dye staining and the pattern of vessel development and maturation was then monitored. The importance of lateral flow was confirmed using several approaches: (1) capacity for lateral flow, (2) effect of increasing the distance of water transport, and (3) effect of ion concentrations. Living vessel elements were found along the developing bundles, they occupied a significant proportion of the distal and peripheral parts of the flow path, forming a substantial barrier to apoplastic water flow. Water in the developing xylem bundles could move easily from vessel to vessel and between secondary and primary xylem. Furthermore, data from increasing the transport length and altering the ion concentrations supported the critical contribution of the lateral flow to the total hydraulic conductance within the developing bundles. The hydraulic architecture of the developing xylem bundles is described. The results are discussed in terms of reliability and efficiency of water transport during shoot growth and development.